Reinhardt Walter, Dolff Sebastian, Benson Sven, Broecker-Preuß Martina, Behrendt Stefan, Hög Antonia, Führer Dagmar, Schomburg Lutz, Köhrle Josef
1 Department of Nephrology, University Hospital Essen, University Duisburg-Essen , Germany .
2 Institute of Medical Psychology and Behavioral Immunobiology, University Clinic Essen, University Duisburg-Essen , Germany .
Thyroid. 2015 Oct;25(10):1091-6. doi: 10.1089/thy.2015.0097. Epub 2015 Sep 8.
Chronic kidney disease (CKD) impairs thyroid hormone (TH) metabolism and is associated with low serum triiodothyronine (T3) concentrations in patients with a low glomerular filtration rate (GFR). Whether this results from decreased T3 formation from thyroxine (T4) by impaired 5'-deiodinase (DIO) activity and/or enhanced degradation of T3 and increased reverse triiodothyronine (rT3) formation from T4 by elevated 5-DIO activity remains unclear. Both activating 5'- and the inactivating 5-deiodination of TH are catalyzed by three selenium (Se)-dependent DIO isoenzymes. Selenoprotein P (SePP) is the major constituent of serum selenium, and functions as Se transport protein from liver to kidney and several other organs. This study tested the hypothesis that serum SePP and TH status are associated with the degree of renal impairment in patients with CKD.
A total of 180 CKD patients (stages 1-5) and 70 chronic hemodialysis (CHD) patients undergoing hemodialysis three times per week for at least two years were prospectively investigated for clinical data, parameters of renal function, serum TH profile (thyrotropin, T4, free thyroxine [fT4], T3, free triiodothyronine (fT3), rT3, thyroxine-binding globulin [TBG]), C-reactive protein (CRP), and serum SePP.
In CKD patients, renal function was negatively associated with SePP concentration (standardized β = -0.17, p = 0.029); that is, SePP concentrations increased in more advanced CKD stages. In contrast, significantly lower SePP concentrations were found in patients on hemodialysis compared with CKD patients (M ± SD = 2.7 ± 0.8 mg/L vs. 3.3 ± .9 mg/L; p < 0.001). Notably, in CKD patients, the SePP concentration was negatively associated with T4 (standardized β = -0.16, p = 0.039) and fT4 (standardized β = -0.16, p = 0.039) concentrations, but no association was found with T3, fT3, rT3, T3/T4, rT3/T3, rT3/T4, or TBG concentrations. The SePP concentration was also negatively associated with CRP levels (standardized β = -0.17, p = 0.029). In the CHD group, no association was detected between SePP and the investigated TH parameters.
Impaired renal function is positively correlated with serum concentrations of SePP. In patients undergoing CHD treatment, SePP concentrations were significantly reduced, but the TH profile remained unaffected. These findings indicate an important contribution of kidney function on serum SePP homeostasis, and consequently on Se status.
慢性肾脏病(CKD)会损害甲状腺激素(TH)代谢,并且与肾小球滤过率(GFR)降低的患者血清三碘甲状腺原氨酸(T3)浓度降低有关。这是由于5'-脱碘酶(DIO)活性受损导致甲状腺素(T4)生成T3减少和/或T3降解增强以及5-DIO活性升高导致T4生成反三碘甲状腺原氨酸(rT3)增加所致,目前尚不清楚。TH的活化5'-脱碘和失活5-脱碘均由三种硒(Se)依赖性DIO同工酶催化。硒蛋白P(SePP)是血清硒的主要成分,作为从肝脏到肾脏和其他几个器官的硒转运蛋白发挥作用。本研究检验了以下假设:血清SePP和TH状态与CKD患者的肾功能损害程度相关。
前瞻性调查了总共180例CKD患者(1-5期)和70例每周进行三次血液透析至少两年的慢性血液透析(CHD)患者的临床资料、肾功能参数、血清TH谱(促甲状腺激素、T4、游离甲状腺素[fT4]、T3、游离三碘甲状腺原氨酸[fT3]、rT3、甲状腺素结合球蛋白[TBG])、C反应蛋白(CRP)和血清SePP。
在CKD患者中,肾功能与SePP浓度呈负相关(标准化β=-0.17,p=0.029);也就是说,在更晚期的CKD阶段SePP浓度升高。相比之下,与CKD患者相比,血液透析患者的SePP浓度显著降低(M±SD=2.7±0.8mg/L对3.3±0.9mg/L;p<0.001)。值得注意的是,在CKD患者中,SePP浓度与T4(标准化β=-0.16,p=0.039)和fT4(标准化β=-0.16,p=0.039)浓度呈负相关,但与T3、fT3、rT3、T3/T4、rT3/T3、rT3/T4或TBG浓度无相关性。SePP浓度也与CRP水平呈负相关(标准化β=-0.17,p=0.029)。在CHD组中,未检测到SePP与所研究的TH参数之间存在关联。
肾功能受损与血清SePP浓度呈正相关。在接受CHD治疗的患者中,SePP浓度显著降低,但TH谱未受影响。这些发现表明肾功能对血清SePP稳态以及因此对硒状态有重要影响。